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M. Ni, H. Jarstadmarken, M. Holland, G. De Vries; Experimental Choroidal Neovascularization in Rabbits – Angiogenic Molecule Dependent Models . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3930.
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Purpose: We have shown previously that subretinal injection of bFGF and LPS leads to the formation of experimental CNV in rabbits. The purpose of present study was to evaluate the effects of other known pro-angiogenic molecules administered under similar conditions. Methods: Angiogenic molecules including cytokines (IL-1α, IL-1ß, IL-8, TNF-α), endotoxin (LPS), and growth factors (bFGF, VEGF), or a combination of endotoxin (LPS) and growth factors (bFGF or VEGF), were administered by subretinal injection in rabbits. The ability of these molecules to induce CNV was evaluated by monitoring the development and growth of CNV for a period of 4 weeks, using fluorescein angiography. The extent of neovascularization was quantified by image analysis, as well as confirmed by histology. The suitability of good rabbit CNV models for assessing anti-angiogenic agents was appraised by the systemic administration of dexamethasone. Results: The incidence of experimental CNVs induced by these pro-angiogenic molecules varied from 50% to 100%, depending on the type and dose of agent administered. 100 ng of IL-1α, 100 ng of IL-1ß, 1000 ng of TNF-α, 1000 ng of VEGF or cocktails containing 100 ng of LPS and 100 ng of bFGF, or 100 ng LPS and 100 ng of VEGF induced CNV in 100% of the eyes treated. The induction of CNV by IL-8 was less consistent, with responses observed in only 50-60% of eyes evaluated. These experimental CNVs resemble human CNV histologically in that the new vessel growth originates from the choroidal vasculature. In addition, it was observed that the formation and growth of subretinal CNV in these models could be significantly inhibited by dexamethasone.Conclusions: These data suggest that cytokines or growth factors, either alone or in combination with LPS, play critical roles in the development of CNV in rabbits. Future studies of the effect of specific inflammatory cytokines or in combination with growth factors may provide insight into the pathogenesis of CNV in humans. Furthermore, the inhibition observed with dexamethasone in these studies points to the possibility of being able to evaluate effective means of pharmacological intervention.
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